Previous work in our laboratory has demonstrated a factor in plasma of volume expanded dogs which inhibits toad bladder sodium transport and is natriuretic in partially nephrectomized rats. Evidence has been accumulated which suggests that the factor may be a natriuretic hormone. The overall objective of the proposed research is to study the chemical nature, site of origin and physiologic significance of the factor. A method for desalting and concentrating the short circuit current inhibitor using Biogel P-2 has been developed. Using this method as a starting point, purified preparations of the factor will be prepared and an attempt made to determine its chemical nature. The mechanism of the natriuretic effect of the factor will be studied in normal rats and dogs by clearance and micropuncture techniques. New methods of bioassay for the factor will be attempted and further studies will be conducted of technical problems with the toad bladder assay. Further studies of the relationship between extracellular fluid volume, renal sodium excretion and plasma levels of the factor will be conducted. The effect of electrical stimulation of the hypothalamus on urine sodium excretion and plasma antinatriferic activity will be performed. The effect of natriuretic posterior pituitary polypeptides on plasma antinatriferic activity will be examined.